[HTML][HTML] PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ
KA Sheppard, LJ Fitz, JM Lee, C Benander, JA George… - FEBS letters, 2004 - Elsevier
FEBS letters, 2004•Elsevier
Engagement of the immunoinhibitory receptor, programmed death-1 (PD-1) attenuates T-
cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we
demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated
phosphorylation of ZAP70 and association with CD3ζ. In addition, PD-1 signaling attenuates
PKCθ activation loop phosphorylation in a cognate TCR signal. PKCθ has been shown to be
required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C …
cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we
demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated
phosphorylation of ZAP70 and association with CD3ζ. In addition, PD-1 signaling attenuates
PKCθ activation loop phosphorylation in a cognate TCR signal. PKCθ has been shown to be
required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C …
Engagement of the immunoinhibitory receptor, programmed death-1 (PD-1) attenuates T-cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated phosphorylation of ZAP70 and association with CD3ζ. In addition, PD-1 signaling attenuates PKCθ activation loop phosphorylation in a cognate TCR signal. PKCθ has been shown to be required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C-terminal immunoreceptor tyrosine-switch motif (ITSM), acts as a docking site in vitro for both SHP-2 and SHP-1, while the phosphorylated peptide containing the N-terminal PD-1 immunoreceptor tyrosine based inhibitory motif (ITIM) associates only with SHP-2.
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